The projects and activities below are some examples of how CBER is working to accomplish its mission of protecting and enhancing the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies. Many of these projects and activities address goals outlined in the Prescription Drug User Fee Act IV (PDUFA IV) and the 21st Century Cures Act legislation.
FDA regulates pharmaceutical products to ensure a continuous supply of high-quality products in the United States. In regulating the pharmaceutical manufacturing sector, FDA realizes the need for a maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality biologics. To help achieve this vision, the Center for Biologics Evaluation and Research (CBER) encourages the development and adoption of advanced technologies to modernize biopharmaceutical manufacturing. Such a modernization effort aims to result in a more robust manufacturing process with fewer interruptions in production, fewer product failures (before or after distribution), and greater assurance that the biologic products manufactured will provide the expected clinical performance.
In support of this effort, CBER established the CBER Advanced Technologies Program. In September 2018, using its authority under the 21st Century Cures Act, CBER awarded grants to support research projects to study and recommend improvements for the advanced manufacturing of biological products, including the investigation and development of innovative monitoring and control techniques. In addition, the center created the CBER Advanced Technologies Team (CATT) to provide an interactive mechanism within CBER for prospective innovators/developers of advanced technologies to discuss the implementation of these technologies in the development of CBER-regulated biologic products.
CBER launched the Biologics Effectiveness and Safety (BEST) System in October 2017 with the objectives of developing innovative methods to leverage data contained in electronic health records and using natural language processing and artificial intelligence to establish automated adverse event reporting.
The FDA Amendments Act of 2007 directed FDA to develop methods to obtain access to disparate data sources and establish a post-market risk identification system to link and analyze safety data from multiple sources. To meet this mandate FDA established the Sentinel initiative. BEST, the Sentinel System, and FDA-Catalyst form the basis for the overall Sentinel initiative. BEST is also consistent with requirements in the 21st Century Cures Act to implement programs to explore the potential use of real world evidence to support approval of drug and biologics for new indications and to support or satisfy post approval study requirements and with commitments in the Prescription Drug User Fee Act VI (PDUFA VI) to enhance the use of real world evidence for use in regulatory decision making.
See the CBER Biologics Effectiveness and Safety (BEST) System web page for additional information.
Complex and innovative trial designs, such as complex adaptive trials, Bayesian statistical methods, and other novel clinical trial designs, can improve the efficiency or reliability of clinical drug development and can inform regulatory decision making – possibly helping to speed the availability of much-needed drugs and biological products.
As part of FDA’s PDUFA VI commitments, the Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) are conducting the Complex Innovative Designs (CID) Pilot Meeting Program to facilitate highly innovative trial designs. This pilot program provides pharmaceutical and biotech developers the opportunity to engage with senior regulatory staff on clinical trial design proposals. To promote innovation in CID, trial designs developed through the pilot program may be presented by FDA as case studies, such as through a guidance or public workshop. For more information on the pilot program and to learn more about CID, see the FDA Complex Innovative Trials Designs Pilot Program page.
Drug Development Tools (DDTs) are methods, materials, or measures that have the potential to facilitate drug development. Examples of DDTs may include but are not limited to: a biomarker used for clinical trial enrichment, a clinical outcome assessment (COA) used to evaluate clinical benefit, or an animal model used for efficacy testing of medical countermeasures under the regulations commonly referred to as the Animal Rule.
CBER works closely with the Center for Drug Evaluation and Research to implement provisions in the 21st Century Cures Act, PDUFA V and PDUFA VI to facilitate the efficient development of DDTs. This includes establishing a transparent DDT qualification process, making qualified DDTs publicly available, and developing a publicly available list of surrogate endpoints used to support traditional or accelerated drug approvals.
FDA’s Drug Development Tools Qualification Programs website has more information on the DDT qualification processes, and how to submit a DDT to the animal model, clinical outcome assessment, or biomarker qualification program.
FDA’s Qualification Process for Drug Development Tools, Guidance for Industry and FDA Staff provides CBER and CDER’s current thinking with respect to describing the process for requestors interested in qualifying DDTs and on taxonomy for biomarkers and other DDTs.
To facilitate collaborative and innovative drug development tool qualification CBER and CDER have a common submission portal for letters of intent (LOI), qualification packages (QP), and final qualification plans (FQP) for evaluation by the agency. Electronic submissions only: Please send electronic submissions through FDA’s Next Gen Portal. The portal serves as a central location for making submissions, viewing submissions statuses, and reviewing communications from the FDA.
Model-informed drug development (MIDD) utilizes exposure-based, biological or statistical models derived from preclinical and clinical data sources to address drug development or regulatory issues. When successfully applied, MIDD approaches can assist in benefit-risk assessments, improve clinical trial efficiency, increase the probability of regulatory success, and optimize drug dosing or therapeutic individualization.
As part of FDA’s PDUFA VI commitments, the Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) are conducting a pilot MIDD program. Through the pilot program, the FDA aims to work with the sponsor(s) on applying MIDD approaches to product development and the regulatory process.
For more information visit FDA’s Model-Informed Drug Development Pilot Program web page.
The Center for Biologics Evaluation and Research (CBER) implemented Modernized Time Reporting on October 1, 2017. The implementation of this program allows the Center to proactively plan for needed resource levels and allocation of funds. Implementation of Modernized Time Reporting is also a requirement under the PDUFA VI Reauthorization Performance Goals and Procedures FY 2018 – 2022 letter.
The Agency and industry agreed to develop Resource Capacity Planning and Modernized Time Reporting (RCP/MTR) capabilities. An Implementation Plan published March 2018, outlines the approach and timeline for implementing these capabilities. CBER was the first medical product center to implement modernized time reporting and is providing lessons learned and best practices to the other FDA Centers. For more information on the roadmap for RCP/MTR pursuant to the Agency’s commitment, please see the Resource Capacity Planning & Modernized Time Reporting Implementation Plan.
Patient input is a critical part of CBER’s understanding of diseases and conditions. Engaging with patients and listening to their perspectives on their diseases and treatments may help us advance patient-focused medical product development. Supported by provisions in both the 21st Century Cures Act of 2016 and PDUFA VI, authorized under the Food and Drug Administration Re-authorization Act (FDARA) in 2017, CBER’s patient engagement program is committed to incorporating patient involvement in the center’s regulatory work. See the Center for Biologics Evaluation and Research Patient Engagement Program web page for additional information.
The CBER Rare Disease Program engages and supports CBER staff in focused rare disease activities such as training, outreach and policy development to enhance the Center’s capacity to accelerate the development and approval of biologics for rare diseases. The program also conducts focused analyses of CBER regulatory data concerning biologics development programs or biologics approvals for rare diseases. The CBER Rare Disease Program conducts, tracks and reports on these activities to meet PDUFA VI regulatory commitments, authorized under the Food and Drug Administration Re-authorization Act (FDARA) in 2017.
CBER Rare Disease Program collaborates with the FDA Office of Orphan Products Development (OOPD) and other FDA rare disease staff from the Center for Devices and Radiological Health (CDRH) and the Center for Drug Evaluation and Research (CDER) to share knowledge and expertise and to address cross-center issues. See the FDA web page Developing Products for Rare Diseases and Conditions for more information on OOPD and FDA’s rare disease programs.
Regenerative medicine is a rapidly expanding, innovative field that has the potential to treat serious conditions, particularly in patients with unmet medical needs. CBER regulates a variety of regenerative medicine therapies including cell therapies, certain xenogeneic cell therapies, certain gene therapies, tissue-engineered products, and certain combination products.
For more information regarding CBER’s roles and activities related to the development of regenerative medicine products, including FDA’s regulatory framework for regenerative medicine products, CBER’s implementation of the regenerative medicine advanced therapy (RMAT) designation program in accordance with the 21st Century Cures Act, and CBER fellowship and research programs focused on regenerative medicine, see CBER’s Resources Related to Regenerative Medicine Therapies page.